STIMULUS-MDS1 Trial: Sabatolimab and HMA Falls Short in Higher-Risk MDS

Primary results from the ongoing phase 2 STIMULUS-MDS1 trial ( Identifier: NCT03946670) showed that sabatolimab (MBG453), a novel TIM3-targeted immunotherapy, plus HMA did not significantly improve PFS compared with placebo (11.1 months vs. 8.5 months; P =.102) in patients with intermediate-risk, high-risk, and very-high risk MDS.3

The rate of complete response (CR) plus partial remission and hematologic improvement was 49.2% with sabatolimab-HMA and 37.1% with placebo. The CR rate was 23.1% and 21.0%, respectively. The median duration of CR was 18.0 months and 9.2 months, respectively. The median OS was 19.0 months and 18.0 months, respectively (HR, 0.905).

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“While improvements in the primary endpoint measures were not statistically significant, longer assessment may suggest a delayed onset benefit for patients who were given sabatolimab,” said study presenter Amer M. Zeidan, MD, of Yale University in New Haven.

“The ongoing phase 3 STIMULUS-MDS2 trial with a primary endpoint of OS has completed accrual and will definitively determine on the impact of sabatolimab in higher-risk MDS patients,” he concluded.

SINTRA-REV Trial: Low-Dose Lenalidomide Lowers Risk of Transfusion Dependency, Improves Responses

Final results from the phase 3 SINTRA-REV trial ( Identifier: NCT01243476) showed that, compared with placebo, low-dose lenalidomide prolonged time to transfusion, lowered the risk of transfusion dependency, and demonstrated no increase in progression rate or clonal evolution in patients with low-risk MDS.

At a median follow-up of 5.05 years, low-dose lenalidomide lowered the risk of transfusion dependency by 69.8% (HR, 0.302; P =.005). With respect to erythroid response, patients treated with low-dose lenalidomide had a 77.8% response compared with 0% for placebo. In terms of cytogenetic response, patients in the lenalidomide group had a response of 94.1% compared with 0% for placebo.

“The median time to transfusion dependency was not reached for patients who received lenalidomide compared with 11.6 months in those who received placebo,” said study presenter Maria Diez-Campelo, MD, of Hospital Universitario de Salamanca-IBSAL in Salamanca, Spain.

The rate of grade 3/4 neutropenia was 44.7% in patients treated with low-dose lenalidomide and 4.8% in those who received placebo. However, the researchers noted that low-dose lenalidomide did not cause clinically relevant neutropenia.

“Based on the results, we confirm that early treatment with low-dose lenalidomide prolonged the time and reduced the risk of transfusion dependency, with promising responses and an acceptable safety profile,” Dr Diez-Campelo concluded.

Disclosures: The ASCERTAIN trial was sponsored by Astex Pharmaceuticals. The MEDALIST trial was sponsored by Celgene and Acceleron Pharma. STIMULUS-MDS1 was sponsored by Novartis. The SINTRA-REV trial was co-sponsored by Fundación General de la Universidad de Salamanca and Celgene. Please see the original references for a full list of disclosures.


1. Savona MR, McCloskey JK, Griffiths EA, et al. Prolonged survival in bi-allelic TP53-mutated (TP53mut) MDS subjects treated with oral decitabine/cedazuridine in the ascertain trial (ASTX727-02). Presented at ASH 2022; December 10-13, 2022. Abstract 854.

2. Santini V, Fenaux P, Zeidan AM, et al. Overall survival and progression-free survival of patients following luspatercept treatment in the MEDALIST trial. Presented at ASH 2022; December 10-13, 2022. Abstract 1774.

3. Zeidan AM, Ando K, Rauzy O, et al. Primary results of stimulus-MDS1: a randomized, double-blind, placebo-controlled phase II study of TIM-3 inhibition with sabatolimab added to hypomethylating agents (HMAs) in adult patients with higher-risk myelodysplastic syndromes (MDS). Presented at ASH 2022; December 10-13, 2022. Abstract 853.

4. Cadenas FL, Lumbreras E, Gonzalez T, et al. Evaluation of lenalidomide (len) vs placebo in non-transfusion dependent low risk del(5q) MDS patients. Final results of Sintra-REV phase III international multicenter clinical trial. Presented at ASH 2022. December 10-13, 2022. Abstract 460.